More than 28 million Americans-about 10% of the population-have impaired hearing. Noise-induced hearing loss (NIHL) continues to be the primary cause of acquired hearing loss in the industrialized world and chemotherapy ototoxicity also contributes. Compelling studies on nervous tissue and exciting new results in the inner ear have provided a better understanding of the mechanisms underlying noise-induced damage of the ear. Our proposed Phase I study will investigate two pharmaceuticals in an animal model for subsequent human trials in Phase II. Reactive oxygen species (ROS) are implicated as an initiator of the cell death cycle in cochlear tissues. Histologic, biochemical and auditory evidence support the ROS-mediated NIHL hypothesis. Endogenous glutathione (GSH) is a potent free radical scavenger, and supplementation strategies have demonstrated a protective role. Mass Trace has licensed two pharmaceuticals that directly or indirectly supplement glutathione. These compounds include a cysteine prodrug (cysteine is thought to be a rate limiting peptide for GSH synthesis), and a glutathione ester that demonstrates better intracellular bioavailability than free GSH. Each of these compounds has completed toxicology testing in humans for other clinical indications, so success in the proposed studies could lead to rapid initiation of human clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE